Why Are Computational Neuroscience and Systems Biology So Separate?

Despite similar computational approaches, there is surprisingly little interaction between the computational neuroscience and the systems biology research communities. In this review I reconstruct the history of the two disciplines and show that this may explain why they grew up apart. The separation is a pity, as both fields can learn quite a bit from each other. Several examples are given, covering sociological, software technical, and methodological aspects. Systems biology is a better organized community which is very effective at sharing resources, while computational neuroscience has more experience in multiscale modeling and the analysis of information processing by biological systems. Finally, I speculate about how the relationship between the two fields may evolve in the near future

The principle of recursive genome function. The Principle of Recursive Genome Function

Abstract Responding to an open request, the principle of recursive genome function (PRGF) is put forward, effectively reversing two axioms of genomics as we used to know it, prior to the Encyclopedia of DNA Elements Project (ENCODE). The PRGF is based on the reversal of the interlocking but demonstrably invalid central dogma and "Junk DNA" conjectures that slowed down the advance of sound theory of genome function, as far as information science is concerned, for half a century. PRGF illustrates the utility of the class of recursive algorithms as the intrinsic mathematics of post-ENCODE genomics. A specific recursive algorithmic approach to PRGF governing the growth of the Purkinje neuron is sketched, building the structure in a hierarchical manner, starting from primary genomic information packets and in each recursion using auxiliary genomic information packets, cancelled upon perusal. The predictive power of the principle and its experimental support are indicated. It is argued that genomics is no longer an exceptional instance of the applicability of recursion throughout the sciences

Coordinate Dependence of Variability Analysis

Analysis of motor performance variability in tasks with redundancy affords insight about synergies underlying central nervous system (CNS) control. Preferential distribution of variability in ways that minimally affect task performance suggests sophisticated neural control. Unfortunately, in the analysis of variability the choice of coordinates used to represent multi-dimensional data may profoundly affect analysis, introducing an arbitrariness which compromises its conclusions. This paper assesses the influence of coordinates. Methods based on analyzing a covariance matrix are fundamentally dependent on an investigator's choices. Two reasons are identified: using anisotropy of a covariance matrix as evidence of preferential distribution of variability; and using orthogonality to quantify relevance of variability to task performance. Both are exquisitely sensitive to coordinates. Unless coordinates are known a priori, these methods do not support unambiguous inferences about CNS control. An alternative method uses a two-level approach where variability in task execution (expressed in one coordinate frame) is mapped by a function to its result (expressed in another coordinate frame). An analysis of variability in execution using this function to quantify performance at the level of results offers substantially less sensitivity to coordinates than analysis of a covariance matrix of execution variables. This is an initial step towards developing coordinate-invariant analysis methods for movement neuroscience.National Science Foundation (BCS-0096543 and PAC-0450218 )National Institutes of Health (R01HD045639 )New York State Spinal Cord Injury Center of Research Excellence (CO19772)Toyota Motor Company's Partner Robot DivisionEric P. and Evelyn E. Newman Fun

Mechanisms of human cerebellar dysmetria: experimental evidence and current conceptual bases.

The human cerebellum contains more neurons than any other region in the brain and is a major actor in motor control. Cerebellar circuitry is unique by its stereotyped architecture and its modular organization. Understanding the motor codes underlying the organization of limb movement and the rules of signal processing applied by the cerebellar circuits remains a major challenge for the forthcoming decades. One of the cardinal deficits observed in cerebellar patients is dysmetria, designating the inability to perform accurate movements. Patients overshoot (hypermetria) or undershoot (hypometria) the aimed target during voluntary goal-directed tasks. The mechanisms of cerebellar dysmetria are reviewed, with an emphasis on the roles of cerebellar pathways in controlling fundamental aspects of movement control such as anticipation, timing of motor commands, sensorimotor synchronization, maintenance of sensorimotor associations and tuning of the magnitudes of muscle activities. An overview of recent advances in our understanding of the contribution of cerebellar circuitry in the elaboration and shaping of motor commands is provided, with a discussion on the relevant anatomy, the results of the neurophysiological studies, and the computational models which have been proposed to approach cerebellar function.Journal ArticleResearch Support, Non-U.S. Gov'tReviewSCOPUS: ar.jinfo:eu-repo/semantics/publishe

The Cerebellum, Cerebellar Disorders, and Cerebellar Research—Two Centuries of Discoveries

Research on the cerebellum is evolving rapidly. The exquisiteness of the cerebellar circuitry with a unique geometric arrangement has fascinated researchers from numerous disciplines. The painstaking works of pioneers of these last two centuries, such as Rolando, Flourens, Luciani, Babinski, Holmes, Cajal, Larsell, or Eccles, still exert a strong influence in the way we approach cerebellar functions. Advances in genetic studies, detailed molecular and cellular analyses, profusion of brain imaging techniques, emergence of behavioral assessments, and reshaping of models of cerebellar function are generating an immense amount of knowledge. Simultaneously, a better definition of cerebellar disorders encountered in the clinic is emerging. The essentials of a trans-disciplinary blending are expanding. The analysis of the literature published these last two decades indicates that the gaps between domains of research are vanishing. The launch of the society for research on the cerebellum (SRC) illustrates how cerebellar research is burgeoning. This special issue gathers the contributions of the inaugural conference of the SRC dedicated to the mechanisms of cerebellar function. Contributions were brought together around five themes: (1) cerebellar development, death, and regeneration; (2) cerebellar circuitry: processing and function; (3) mechanisms of cerebellar plasticity and learning; (4) cerebellar function: timing, prediction, and/or coordination? (5) anatomical and disease perspectives on cerebellar function.Historical ArticleJournal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe